Genetic mutagenesis and biochemical approaches have been employed to study the role of ras oncogenes in cell transformation and ras proto-oncogenes in normal cell function. By site-directed mutagenesis of the H-ras oncogene at the NKXD consensus motif of the GTP-binding site, we have identified several mutants derived from the viral H-ras oncogene by substituting the asparagine-116 residue with tyrosine and isoleucine that are trans-dominant suppressors of ras activities. Studies are in progress to delineate ras functions employing these dominant negative mutants of ras oncogenes.